Fig. 8. Schematic diagram illustrating NHE1 mediated mechanisms in regulation of LCN2 expression and release from stroke-induced RA.

Ischemia stimulates NHE1 expression and activation in RA. Overstimulation of NHE1 activity leads to increased NOX mediated ROS production and NF-κB activation which induces LCN2 gene expression. Increased release of LCN2⁺ exosomes from RA induces neurodegeneration and neuronal apoptosis. Astrocyte specific deletion of Nhe1 reduced LCN2 induced neuronal loss and neurodegeneration by inhibiting LCN2⁺ exosome release from RA.